Reactive oxygen species: oxidative damage and pathogenesis

Abstract

Reactive oxygen species (ROS) such as O₂^–, H₂O₂ and OH are highly toxic to cells. Cellular antioxidant enzymes, and the free-radical scavengers normally protect a cell from toxic effects of the ROS. However, when generation of the ROS overtakes the antioxidant defense of the cells, oxidative damage of the cellular macromolecules (lipids, proteins, and nucleic acids) occurs, leading finally to various pathological conditions. ROS-mediated lipid peroxidation, oxidation of proteins, and DNA damage are well-known outcomes of oxygen-derived free radicals, leading to cellular pathology and ultimately to cell death. The mechanism of ROS-mediated oxidative damage of lipids, proteins, and DNA has been extensively studied. The site-specific oxidative damage of some of the susceptible amino acids of proteins is now regarded as the major cause of metabolic dysfunction during pathogenesis. ROS have also been implicated in the regulation of at least two well-defined transcription factors which play an important role in the expression of various genes encoding proteins that are responsible for tissue injury. One of the significant benefits of the studies on ROS will perhaps be in designing of a suitable antioxidant therapy to control the ROS-mediated oxidative damage, and the disease processes.